The requirements for abuse-deterrent opioids are in flux as the FDA grapples with what they can do to address the ongoing opioid epidemic. As part of their efforts in promoting the development of abuse-deterrent opioids, the Agency has required that manufacturers demonstrate that their product is able to demonstrate a real-world impact on abuse. The problem that has arisen from this requirement is that demonstrating a real-world impact on abuse is a moving target as social awareness, public policy, and product availability shift on a local, regional, and national basis.

The FDA convened a panel of experts to evaluate “Data and Methods for Evaluating the impact of opioid formulations with properties designed to deter abuse in the postmarket setting.” The goal of this meeting was to get input from a widely varying group of experts on what is possible, what is reasonable to require from product manufacturers, and what is the real goal of such research requirements.

New Efforts with REMS Requirements

FDA Commissioner, Dr. Scott Gottlieb, kicked off the discussion with opening comments highlighting the importance of opioid abuse both to the FDA and to the wider administration. Dr. Gottlieb outlined his goals for the FDA in the fight against opioid abuse and misuse and noted that the REMS requirements for Extended Release (ER)/ Long-Acting (LA) opioids are now going to be added to the Immediate Release (IR) opioids as well. This will have a significant impact on the development, and more importantly, on the post-approval requirements for IR opioids. These developments are not a real surprise since the Agency has clearly been moving in this direction for a while now.

The Abuse-Deterrent Labeling Claim

For drug manufacturers, the reason the coveted “abuse-deterrent” drug labeling claim that these studies are required to support is so important is that payers have made it clear that they will not add abuse-deterrent opioids to their formularies or preferred drug lists until a product is granted this labeling claim by the FDA. Reimbursement has plagued these products as demonstrated by the very low level of market penetration by the currently approved abuse-deterrent opioid formulations. The developers need the cooperation of payers to ensure access to a market largely comprised of non-abuse-deterrent generic formulations.

Some interesting learnings that came from the expert discussion include the following:

• The FDA and experts agree that they cannot and should not be responsible for the shift from prescription opioids to other illicit opioid drugs such as heroin. The overall opioid problem is a societal problem and expands well beyond the purview of the FDA.
• Similarly, the experts seemed to agree that the perceived path to abuse starting with treatment of acute pain following a surgery or injury and leading to injecting heroin is far more rare than you would expect by reading advocate and news updates on the subject. That is not to say that this never happens, simply that there are a variety of paths to opioid abuse.
• Further, the experts agree that abuse-deterrent opioid formulations are not intended, and should not be expected, to slow the progression of physical tolerance or dependence on opioid drugs.

The goal of these products is to resist the progression to alternate routes of administration, such as snorting or injecting, depending upon the formulation and the labeling claims approved for each product.

Post-Approval Requirements for Abuse-deterrent Opioid Formulations

The overall impact of this meeting on the post-approval requirements for abuse-deterrent opioid formulations is not yet clear. However, the experts and the FDA did appear to agree that the scope of such studies should be focused on what can realistically be demonstrated for a given product based on its intended impact on abuse. Developers of abuse-deterrent products should expect extensive post-approval requirements and that the Agency will be highly engaged in the development of those post-approval studies, at least in the foreseeable future.

For the latest expert guidance on abuse-deterrent formulations, contact us.